USMLE® Step 1 Question of the Day: Neuroleptic Malignant Syndrome

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This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case focuses on a 23-year-old man who collapsed and started having tremors in the upper and lower extremities during a festival. Can you figure it out?

A 23-year-old man is brought to the emergency department after collapsing at a music festival on a hot summer day. The patient was with friends at an electronic dance show. According to his friends, the patient consumed a powdered drug at the concert. Afterward, while dancing, he suddenly collapsed and started having tremors in the upper and lower extremities. He has a past medical history of depression, anxiety, and bipolar disorder, for which he takes fluoxetine, alprazolam as needed, and aripiprazole. Temperature is 39.0°C (102.2 °F), pulse is 132/min, respirations are 24/min, blood pressure is 172/85 mmHg, and O2 saturation is 97% on room air. On physical examination, the patient is diaphoretic, mumbling incoherent sounds, and will not lie still on the gurney. The patient has increased muscle tone. Brief, sudden jerks are present throughout the upper and lower extremities. Which of the following clinical features is most specific to this patient’s clinical presentation?

A. Myoclonus

B. Hyperthermia

C. Tachycardia

D. Increased muscle tone

E. Encephalopathy 

The correct answer to today’s USMLE® Step 1 Question is…

A. Myoclonus

Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

The incorrect answers to today’s USMLE® Step 1 Question are…

B. Hyperthermia 

Incorrect: Hyperthermia is observed in both neuroleptic malignant syndrome and serotonin syndrome. However, the hyperthermia in neuroleptic malignant syndrome tends to be more exaggerated, and patients may have body temperatures exceeding 104°F (40°C). 

C. Tachycardia

Incorrect: Tachycardia is observed in both neuroleptic malignant syndrome and serotonin syndrome.. As a result, this finding is not specific to either condition. 

D. Increased muscle tone

Incorrect: Muscle tone and rigidity are often observed in both neuroleptic malignant syndrome and serotonin syndrome. However, muscle rigidity is often much more severe in patients with neuroleptic malignant syndrome. 

E. Encephalopathy 

Incorrect: Encephalopathy is a feature of both neuroleptic malignant syndrome and serotonin syndrome. This clinical finding does not aid in the differentiation of these conditions. 

Main Explanation

This patient has multiple findings concerning serotonin syndrome, including autonomic instability, hyperthermia, altered mental status, and myoclonus. Among these findings, the one most specific for serotonin syndrome is myoclonus, which is absent in a similar condition, neuroleptic malignant syndrome. 

Serotonin syndrome is a potentially life-threatening condition resulting from increased serotonergic activity of the central nervous system. The condition most commonly arises when multiple psychoactive compounds affecting serotonin are ingested simultaneously or in excess. The patient in this vignette likely consumed a stimulant drug (e.g., ecstasy, cocaine, amphetamines) while at the music show. This drug, in combination with his prescribed fluoxetine, resulted in the onset of serotonin syndrome. 

Clinically, the condition is characterized by increased neuromuscular activity (e.g., myoclonus, hyperreflexia, hypertonia) and autonomic instability (e.g., hyperthermia, diaphoresis). Additional findings include altered mental status, mydriasis, and ocular clonus. 

Treatment is largely supportive and includes targeted temperature management, administration of intravenous fluids, correction of electrolyte disturbances, and benzodiazepines as needed. Historically, the medication cyproheptadine was recommended for treatment. However, this medication has largely fallen out of favor due to its limited efficacy in subsequent research trials.

Major Takeaway 

Serotonin syndrome is a potentially life-threatening condition resulting from increased serotonergic activity of the central nervous system. A distinguishing feature of this condition is the presence of myoclonus, which is absent in neuroleptic malignant syndrome. 

References 

Birmes, P., Coppin, D., Schmitt, L., Lauque, D. (2003) Serotonin syndrome: A brief review. CMAJ. 168, 1439-1442. PMID: 12771076.

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